The present invention relates to novel 2-pyridinecarbothioamides. More particularly, it relates to novel 2-pyridinecarbothioamides which have inhibitory activity on ulcers, to processes for preparation thereof, to pharmaceutical compositions comprising the same, and to the method of using the same therapeutically in the treatment of ulcers in human beings and animals.
The compounds of the present invention have the following formula: ##STR1## wherein R.sup.1 is fluorine, R.sup.2 and R.sup.3 are each hydrogen or fluorine, and R.sup.4 is hydrogen or lower alkyl.
The closest prior art is German Patent No. 953,635 (1956) and E. A. Popova et al, Deposited Doc. 1981, SPSTL 586 Khp-D81. They disclose a number of 2-pyridinecarbothioamides as intermediates in the preparation of therapeutics and bactericidal agents, respectively. However, the compounds of the present invention are not exemplified in the numerous examples contained in the two above mentioned references.
Although the mechanism of cytoprotection is not clearly defined yet, there is a suggestion that it may be partially mediated through the release of gastric mucosal prostaglandins, (Hollander et al, Gastroenterology 86: 1114, 1984 and Tarnawski et al, Gastroenterology 86: 1276, 1984). Szelenyi et al, (Gastroenterology 88: 1604, 1985) has suggested non-prostaglandin mediated mechanisms for cytoprotection.
Activity in the ethanol induced ulcer model is an indication of cytoprotection, regardless of the antisecretory characteristics of the drug. Antisecretory agents, such as the H.sub.2 receptor antagonist cimetidine and the anticholinergic agent propantheline bromide do not protect in this model. See Robert et al, Scand. J. Gastroenterol. 19 (Suppl. 101): 69-72, 1984.
The compounds of this invention have been found to possess effective gastric and duodenal cytoprotective properties. These properties along with a relatively low order of toxicity, render these compounds valuable agents for treating ulcers in humans and animals.